Wu Cheng-Ta, Lin Rio L C, Sung Pei-Hsun, Kuo Feng-Chih, Yip Hon-Kan, Lee Mel S
Department of Orthopaedic Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.
Department of Medicine, Division of Cardiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.
J Clin Med. 2022 Aug 24;11(17):4963. doi: 10.3390/jcm11174963.
Genetic polymorphism of nitric oxide synthase (NOS) can cause reduction of nitric oxide (NO) levels and may be associated with osteonecrosis of the femoral head (ONFH). However, the association of coagulopathy and NOS polymorphism in ONFH patients has not been confirmed. Between November 2005 and October 2013, 155 patients with ONFH were recruited in the study of serum coagulation profiles and NOS polymorphism. Another 43 patients who had dysplasia, osteoarthritis, or trauma of hip joints were included as controls. PCR genotyping for the analysis of NOS 27-bp polymorphism in intron 4 was performed. The analysis of coagulation profiles included fibrinogen, fibrinogen degradation product (FDP), protein S, protein C, and anti-thrombin III. The results showed that 27-bp repeat polymorphism was significantly associated with ONFH (OR 4.32). ONFH patients had significantly higher fibrinogen, FDP, protein S, and anti-thrombin III levels than that of the controls. The incidence of coagulopathy was significantly higher in ONFH patients (73.2%), and the odds ratio increased from 2.38 to 7.33 when they had 27-bp repeat polymorphism. Patients with hyperfibrinogenemia, elevated FDP levels, and with the risk factor of alcohol or steroid use had significantly higher risks of bilateral hip involvement. This study demonstrated the presence of NOS polymorphism, and a resultant reduction in NO production was associated with coagulopathy, which in turn might contribute to higher risks of bilateral ONFH. Our data suggests that checking NOS polymorphism and coagulopathy may provide a new avenue in managing ONFH.
一氧化氮合酶（NOS）的基因多态性可导致一氧化氮（NO）水平降低，并可能与股骨头坏死（ONFH）相关。然而，ONFH患者中凝血病与NOS多态性之间的关联尚未得到证实。在2005年11月至2013年10月期间，155例ONFH患者被纳入血清凝血谱和NOS多态性研究。另外43例患有髋关节发育不良、骨关节炎或创伤的患者作为对照。进行聚合酶链反应（PCR）基因分型以分析第4内含子中的NOS 27-bp多态性。凝血谱分析包括纤维蛋白原、纤维蛋白原降解产物（FDP）、蛋白S、蛋白C和抗凝血酶III。结果显示，27-bp重复多态性与ONFH显著相关（比值比4.32）。ONFH患者的纤维蛋白原、FDP、蛋白S和抗凝血酶III水平显著高于对照组。ONFH患者中凝血病的发生率显著更高（73.2%），当他们具有27-bp重复多态性时，比值比从2.38增加到7.33。患有高纤维蛋白原血症、FDP水平升高以及有酒精或类固醇使用危险因素的患者双侧髋关节受累的风险显著更高。本研究证明了NOS多态性的存在，并且由此导致的NO产生减少与凝血病相关，这反过来可能导致双侧ONFH的风险更高。我们的数据表明，检测NOS多态性和凝血病可能为ONFH的管理提供一条新途径。
